There is substantial interest in applying proteomics to cancer biomarker discovery. Proteomics is particularly suited for profiling biological fluids and uncovering circulating markers and is currently being applied to the identification of novel biomarkers for breast cancer. Novel proteomic approaches include direct profiling of serum using mass spectrometry, application of a variety of strategies to harness immunity for cancer diagnosis, protein tagging to capture subproteomes rich in diagnostic markers, the use of protein microarrays, and the use of multi-dimensional liquid protein separation technologies for comprehensive profiling of serum and other biological fluids. It is likely that the application of a wide range of proteomics tools to breast cancer will yield a panel of markers that have utility for breast cancer diagnosis.